Tue February 14, 2012

Caregivers Press For Experimental Alzheimer's Drug

A recent study finds that a drug approved by the FDA to treat skin cancer in humans has reversed signs of Alzheimer's in mice and improvements showed up quickly. Neuroscientist Gary Landreth, one of the co-authors of the study, described that on TALK OF THE NATION: SCIENCE FRIDAY last week.

(SOUNDBITE OF ARCHIVED BROADCAST)

DR. GARY LANDRETH: One of the other bits in this story is that if we looked at mice, at Alzheimer's mice, with extensive plaque deposition within their brains, what we observed was that the plaques were removed. We lost about 50 percent of the plaques within 72 hours.

CONAN: Obviously, researchers hope that what works in mice will work safely in humans, but there have to be tests to make sure it works, and that it's not dangerous. Even so, Alzheimer's research and advocacy groups report they're getting calls from caregivers and patients desperate to try this drug. So, doctors, are you getting pressure from patients and caregivers who don't want to wait? 800-989-8255. Email us, talk@npr.org. You can also join the conversation on our website. That's at npr.org. Click on TALK OF THE NATION.

Dr. Jason Karlawish is a professor of medicine and medical ethics at the University of Pennsylvania, where he's also a researcher with the Alzheimer's Disease Center. He joins us by phone from his office in Philadelphia. Nice to have you back on the program.

DR. JASON KARLAWISH: A pleasure to be here, Neal. Thank you.

CONAN: We should note this is not the first time Alzheimer's has been cured in mice, but that not all these remedies that are effective in mice prove effective in humans.

KARLAWISH: That's right. That's right. We've made a lot of progress in treating Alzheimer's in mice. And though we're still striving to make similar progress in treating it in humans, nevertheless, these kinds of studies are very important and very essential before we go to humans.

CONAN: Yet, I think you could probably understand someone with Alzheimer's or somebody treating somebody with Alzheimer's saying tests in humans could take three, four, five years. I'm not going to be around to wait.

KARLAWISH: Yeah. I know. And that's frustrating. But there's - that the time to move from animal to human and then through the trials that involved humans does take several years. And there's just simply no way, right now, the science doesn't allow us to do it any quicker.

CONAN: It is perfectly legal for a doctor to prescribe it, off label, for something else.

KARLAWISH: Right. And that's the challenge here. And prima facie, the question, I think, a competent clinician has to sort of ask himself, herself is, you know, when a family approaches them about this drug that's available for another indication, is, well, what's the data about this drug for a different indication, which is the treatment of Alzheimer's disease? And when they look in the literature or ask their colleagues, they'll find that there's scant data at all, about how to dose it for the adequate safe treatment - effective treatment of a person with Alzheimer's disease.

And essentially what's needed is research, research to figure out what is the safe dose and what is a - is it effective? I think, though, that when a family does come to you and asks about this, there's a deeper issue going on there, and a regional clinician ought to engage the family on what's motivating them to ask you about this. I mean, they understand it's risky, and probably the empathetic thing to do is to talk with them about other ways that they can channel that emotion and that willingness to take risks, like looking at the clinical trials that are available now that are going on.

CONAN: Because there are other drugs that are being tried.

KARLAWISH: Absolutely. There are several drugs in various phases of development now. And one good way to find out about those clinical trials is to reach out to the Alzheimer's Association's TrialMatch. The association has put together a wonderful Internet or 1-800 access database where you can put in your information and find out the kinds of clinical trials in your area that are available. I think that a family and a patient who hear about this drug and, unfortunately, find out that's not available and not useful for treating Alzheimer's, can instead channel that energy into looking into clinical trials that are available through Alzheimer's Association's TrialMatch.

CONAN: This is a skin cancer treatment. And like most cancer treatments, it is not without side effects. So those are things you have to consider too.

KARLAWISH: Well, sure, yes. But, you know, I think that as sort of almost secondary. I, you know, I don't even know what dose you would take to see if it gets into the brains where you could then begin to measure, does it have an effect on the brain that's positive or not? You know, I don't mean to sound like a scientist, but that's such a basic question that we don't even have an answer to. So the first studies that need to be done in humans are studies that would involve a few volunteers who simply we want to get a sense of, you know, what's the drug's penetration into the brain, et cetera.

CONAN: Volunteers, yet people are willing to call up right now and say, sign me up.

KARLAWISH: Yeah. And again, I think we have to recognize, you know, there's a - this is a bad disease, and there has been increasing, fortunately, recognition in the public and in - by national leaders that we need to do something about this. And these telephone calls are telling us something that, you know, people want to see that the health care systems, the NIH, the federal government are responding to their desperation. And I think we're seeing that now. We have a national Alzheimer's plan in place. President Obama announced a substantial increase in funding that will be available to support Alzheimer's research. You know, we have a national network of clinical trials in place with the Alzheimer's Disease Cooperative Study group. But quite frankly, the bottom line is really the bottom line, we need more funding to move this along.

CONAN: The research that's been done in mice, people know these are mice specially bred for this kind of research...

KARLAWISH: Exactly.

CONAN: ...to be as close as possible to their human counterparts, but there is still a big difference between mice and humans.

KARLAWISH: Yeah. Yeah. Unfortunately, you know, mouse models are just that, they're models. They are not the disease. And, for example, these mice were modeled to have amyloid plaques. They don't have the tau tangles that are also part of the Alzheimer's pathology. Nonetheless, mouse models have been very valuable to give us some guidance about what may or may not be a promising intervention in humans.

But again, you know, they have their limitations, and I think this is another example of, we have to recognize both the strengths and limitations of mouse models. Their strengths are they can get us data very quickly. The limitations are, you know, they have a very different way of metabolizing amyloid than humans do. Their genetically engineered even to have - to develop amyloid in the first place. So there are substantial differences between mice, if you will, and men.

CONAN: And could you give us an example of a drug which appeared very promising in mice to treat Alzheimer's that did not work out so well in humans?

KARLAWISH: Well, I think probably the - a good example that folks can look up on the Internet because it was, you know, it occurred during just not too long ago, were the earliest treatments that were developed or the drugs that were developed for removal of amyloid using immune modulation techniques, in other words, antibodies that would grab amyloid and take it out of the brain, and the earliest forms of those compounds were very promising in mice. I mean, they really cleaned up the amyloid, and you saw clear changes in the measures that we make of mouse cognition to show that their brains are doing better, like swimming through a water maze and whatnot to get a platform. Though extremely promising, but, you know, when deployed in humans in the early stage trials showed some real issues with toxicity, such that the earlier compounds had to be reconfigured and reworked.

Now, fortunately, many years later - and it's sad to say unfortunately many years later - those compounds now are very promising, and some of them are - the reworked compounds - are in the last phase of testing. And we'll know within this calendar year whether those compounds were safe and effective in the treatment of patients with mild to moderate Alzheimer's disease. But sadly, of course, you know, the march of science does take time. I mean, it was somewhat decade ago that those first immune-based therapies were tried that were promising in mice, but unsuccessful in humans.

CONAN: We're talking with Dr. Jason Karlawish, the professor of medicine and medical ethics at the University of Pennsylvania, about a study of a skin cancer drug approved by the FDA to treat skin cancer that has also proved promising in the treatment of Alzheimer's, but only promising in studies with mice. And as he just pointed out, there's a long way from being effective or interesting results in mice to being safe and effective for humans. But we want to hear from doctors. Are you hearing from your patients today and in the past few weeks or so about this drug, and what do you tell them? 800-989-8255. Email: talk@npr.org.

We have an email question from David in St. Louis: Aren't there some skin cancer patients with Alzheimer's? Can't we find them and study them?

KARLAWISH: That's a great question. David's probably had some training in epidemiology maybe. You know, one thing one could look at would be a database that has a collection of individuals with skin cancers who have received this drug or not - and not received it, and look at whether there was a change in the risk of developing Alzheimer's disease or the progression of it, although it'd be hard to see that measured in the database, but yeah.

I mean, one of the approaches to seeing - to looking at the validity of this drug is the basic science models, obviously, which we're seeing with mice, early phase studies in humans are obviously essential, but also let's look at what data are in existing databases that might describe whether this drug and drugs like it might be beneficial for reducing the risk of developing Alzheimer's disease. That would not be adequate data to then say we're ready to go to humans, but it would certainly be data to add to the case that this is a promising drug and worth studying.

CONAN: Let's go next to Anna(ph). Anna with us from Rochester in New York.

ANNA: Hi. I - my grandmother died of Alzheimer's disease last year, and my grandfather was just diagnosed last week, and I've had a lot of experience in the caretaking of both of them. And my question is this - I could be wrong, but I'm wondering - I remember reading about the Salk vaccine that, you know, there were a lot of questions about its safety and, you know, whether it should be used and stuff. But there was also an understanding that this was an epidemic and that it needed to be dealt with. And I guess having seen the effects of Alzheimer's firsthand and knowing that it's a death sentence, this is - I think I'm pretty positive that my grandmother would have given anything in the world if there had just been just a chance that something might have worked. And I guess I'll just take your comments off the air. Thank you very much.

CONAN: OK, Anna. Thanks very much. Of course, she's referring back to the polio vaccine and the panic of the - in the 1950s when that was still so prevalent. And I guess there are some analogies that could also be made to AIDS 10 years ago or so...

KARLAWISH: Sure.

CONAN: ...and the great pressure put on NIH and other institutions to speed up research on AIDS drugs.

KARLAWISH: Yeah. I think those are two good histories to look at and to try and learn from. I mean, we did do studies of the polio vaccine, though. I mean, evidence was required to show that the vaccine reduced the chances of developing polio. It was not simply prescribed without data. What's stunning and fascinating is how people stood in line to join those studies. The tremendous outpouring of national interest and enthusiasm to conquer polio using science is a model for I think just the feelings that the caller has, that there's a lot of interests and enthusiasm out there, and we need to get people into trials.

And to get people into trials, we need to have the resources to do that. I mentioned earlier that the Alzheimer's Association's TrialMatch. The federal government has ClinicalTrials.gov where you can look up studies, but it's all very well to find these studies, we have to have sites that are doing these studies, and so that gets back to a very basic resource, which is money and time. You know, we need a national investment in Alzheimer's disease research that is equivalent to the kind of investments that we put into other devastating diseases such as cancer and cardiovascular disease where I think, over time, we have seen real progress.

You mentioned though, Neal, AIDS. I think AIDS is a good example also where, initially, a devastating, utterly frightening disease, still certainly is frightening, but certainly less devastating as a result of the progress made with research courtesy of both public and private investments. What's interesting in the history of AIDS, of course, is how involved the patients were in helping to shape those clinical trials so that they gathered valid data, but at the same time also respected the rights and interests of those patients. And they made some real contributions to study design that the scientists alone were not able to make. And I think there are similar models that could be thought about with Alzheimer's disease.

CONAN: Dr. Jason Karlawish. You're listening TALK OF THE NATION from NPR News. And let's get to Matt, and Matt's on the line with us from Farmington Hills in Michigan.

MATT: Hi. I'm a neurologist practicing in the Detroit area, and I get a lot of patients whose family members asking me about these trials; they've read about it in a magazine and things like that.

CONAN: And what do you have to tell them?

MATT: Well, I have to tell them that it's, you know, it's just so preliminary and so early. It would be a great thing if we can possibly do anything to stem the tide of dementia. It's such a hard disease on the patient's family, but it's preliminary, it's early. A lot more trials need to be done. And for most patients studying for some dementia, I'm just concerned that by the time the drug gets out there in a commercial form it'll be too late for the current population.

CONAN: And that's got to be frustrating on both ends.

MATT: It's incredibly frustrating. We've got a handful of drugs out there that we can use right now for dementia of Alzheimer's type, and they don't work particularly well.

KARLAWISH: Matt - it's Matt, right?

CONAN: Yeah.

MATT: Yeah.

KARLAWISH: Yeah. I'm curious. If one of your patients or their family member said, so if we can't get this drug clinically, you can't prescribe it. I understand that. I'd love to be in the study. Where would you send them? What would you do?

MATT: You know, that's a good question. I would love to send them off to a study. I don't really know where any are being done right now. If I could get any resources...

KARLAWISH: Exactly.

MATT: ...I would love to do anything I can to get interested patients involved.

KARLAWISH: Exactly. So this is a great example. I mean, you're one, you know, lone light in the wilderness, but, you know, so to speak, but, you know, let's have HHS and Medicare and the NIH, you know, invest in creating an infrastructure where you can easily refer people to a clinical trial in the Detroit area.

MATT: Exactly. Most of the time I just tell them, well, we can call the local academic centers and see if they have anything going on because I really don't know.

KARLAWISH: Exactly. Exactly. And, you know, and I think your story is a common story, and, you know, this is changeable. It doesn't have to be that way.

CONAN: Matt, thanks very much for the call. Good luck.

MATT: Thanks.

CONAN: And finally, Dr. Karlawish, we're getting calls from some doctors saying, this is a very expensive drug. And, yes, it might be legal to prescribe it off-label, but no insurance company is going to pay for it.

KARLAWISH: Well, yeah. You know, money always is a great way to sort of shut down or open up the access. I think, you know, put aside the money, just the data aren't there, so I would just, you know, it's not even worth getting into the debate about, is it worth the money? But let's just pretend that this drug was shown to work in people with Alzheimer's disease, just wave a wand and clear safety and ethics (unintelligible). It does raise another challenge that Alzheimer's disease therapeutics present to us, which is we're talking about a very prevalent common disease, and that means, therefore, an expensive disease. It's expensive to have it, but it's also expensive to treat it. And if the treatment slows the progression of the disease, it'll extend the life of the people with the disease, and, therefore, the cost of that treatment.

Well, I'm simply raising the issue of we need to attend very closely to the economics of this disease and its treatment as we do to developing better treatments for this disease.

CONAN: Dr. Karlawish, thanks very much for your time.

KARLAWISH: You're very welcome. Thank you, Neal.

CONAN: Jason Karlawish, professor of medicine and medical ethics at the University of Pennsylvania. It's the TALK OF THE NATION from NPR News. Transcript provided by NPR, Copyright NPR.